The studies proposed in this request are designed to investigate T cell dysfunction in autoimmune thyroid disease (both Graves' and Hashimoto's diseases). The specific aims are: (1) To prepare purified thyroid reactive T cells by exposure to autologous thyroid cell monolayers and a variety of defined thyroid antigens. (2) To prepare T cell hybridomas which retain thyroid responsivity by fusion of patients' T cells with a human T cell lymphoblastoid cell line and characterize the resulting clones as described below. (3) To clone the resulting proliferating T cells by limiting dilution and select thyroid reactive clones by assays for antigen binding, proliferative responsiveness, and cell-mediated cytotoxicity. (4) To characterize thyroid reactive T cell clones by examination of their surface antigens, proliferative responses to a variety of thyroid and non-thyroid antigens, their MHC restriction, their influence on B cell secretion of thyroid autoantibodies and their secretion of immunoregulatory molecules. These studies will allow an intimate understanding of the role of the T cell in the initiation and amplification of human autoimmune thyroid disease.